Publications by authors named "Yongwoo Jung"

3 Publications

  • Page 1 of 1

8-(Tosylamino)quinoline inhibits tumour progression through targeting phosphoinositide-3-kinase/Akt pathway.

Pharmazie 2013 Feb;68(2):146-52

Department of Genetic Engineering, Sungkyunkwan University, Suwon, Republic of Korea.

We examined whether 8-(tosylamino)quinoline (8-TQ), a structural analogue of BAY 11-7082, is able to modulate various tumourigenic responses using various in vitro and in vivo experimental conditions. 8-TQ exhibited the strongest suppressive activity on the proliferation of C6, A431, HeLa and MDA-MB-231 cells with IC550 values ranging from 10 to 30 microM. According to the analysis of level of active caspase-3, and morphologies of C6, HeLa and MDA-MB-231 cells, it was revealed that 8-TQ is able to induce apoptosis. Furthermore, this compound strongly diminished the invasion of MDA-MB-231 cells, the migration of HeLa cells, and the new generation of blood vessels under non-toxic conditions. Reduction of the phospho-form levels of intracellular signalling enzymes by 8-TQ strongly indicated that molecular signalling machineries composed of phosphoinositide 3-kinase (PI3K)/phosphoinositide-dependent kinase-1 (PDK1)/Akt and extracellular-signal-regulated kinase (ERK) could be targeted by 8-TQ treatment. Indeed, the specific inhibitors (LY294002 and U0126) of PI3K/PDK1/Akt and ERK showed similar anti-cancer properties to 8-TQ. Finally, 8-TQ intraperitoneally injected suppressed the increase of tumour volume up to 40% compared to vehicle-treated control. Taken together, our results clearly suggest that 8-TQ might have applications as a novel anti-cancer drug or may be served as a lead compound to be further optimized.
View Article and Find Full Text PDF

Download full-text PDF

February 2013

8-(Tosylamino)quinoline inhibits macrophage-mediated inflammation by suppressing NF-κB signaling.

Acta Pharmacol Sin 2012 Aug 16;33(8):1037-46. Epub 2012 Jul 16.

Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.

Aim: The macrophage-mediated inflammatory response may contribute to the development of cancer, diabetes, atherosclerosis and septic shock. This study was to characterize several new compounds to suppress macrophage-mediated inflammation.

Methods: Peritoneal macrophages from C57BL/6 male mice and RAW264.7 cells were examined. Anti-inflammatory activity was evaluated in the cells exposed to lipopolysaccharide (LPS). The mechanisms of the anti-inflammatory activity were investigated via measuring transcription factor activation in response to specific signals and via assaying the activities of the target kinases.

Results: Of 7 candidate compounds tested, 8-(tosylamino)quinoline (8-TQ, compound 7) exhibited the strongest activities in suppressing the production of NO, TNF-α, and PGE(2) in LPS-activated RAW264.7 cells and peritoneal macrophages (the IC(50) values=1-5 μmol/L). This compound (1.25-20 μmol/L) dose-dependently suppressed the expression of the pro-inflammatory genes for iNOS, COX-2, TNF-α, and the cytokines IL-1β and IL-6 at the level of transcription in LPS-activated RAW264.7 cells. 8-TQ (20 μmol/L) significantly suppressed the activation of NF-κB and its upstream signaling elements, including inhibitor of κB (IκBα), IκBα kinase (IKK) and Akt in LPS-activated RAW264.7 cells. In in vivo experiments, oral administration of 20 and 40 mg/kg 8-TQ for 3 d significantly alleviated the signs of LPS-induced hepatitis and HCl/EtOH-induced gastritis, respectively, in ICR mice.

Conclusion: 8-TQ (compound 7) exerts significant anti-inflammatory activity through the inhibition of the Akt/NF-κB pathway, thus may be developed as a novel anti-inflammatory drug.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
August 2012

Cross-regulation between protein L-isoaspartyl O-methyltransferase and ERK in epithelial mesenchymal transition of MDA-MB-231 cells.

Acta Pharmacol Sin 2011 Sep 15;32(9):1165-72. Epub 2011 Aug 15.

Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Korea.

Aim: Protein L-isoaspartyl O-methyltransferase (PIMT) regulates cell adhesion in various cancer cell lines through activation of integrin αv and the PI3K pathway. The epithelial mesenchymal transition (EMT) enables epithelial cells to acquire the characteristics of mesenchymal cells, and to allow them to migrate for metastasis. Here, we examined the relationship between PIMT and EMT with attached or detached MDA-MB 231 cells.

Methods: Human breast cancer cell line MDA-MB-231 cells were maintained in a suspension on poly-HEMA in the presence or absence of PIMT siRNA or ERK inhibitor PD98059. The mRNAs and proteins were analyzed using RT-PCR and immunoblotting, respectively.

Results: During cellular incubation under detached conditions, PIMT, integrin αv and EMT proteins, such as Snail, Slug and matrix metalloproteinase 2 (MMP-2), were significantly increased in correlation with the phosphorylation of ERK1/2. The ERK inhibitor PD98059 (25 μmol/L) strongly suppressed the expression of the proteins and PIMT. Interestingly, PIMT siRNA blocked the phosphorylation of ERK and the expression of the EMT proteins. Additionally, PIMT and ERK phosphorylation were both co-activated by treatment with TGF-β (10 ng/mL) and TNF-α (10 ng/mL).

Conclusion: A tight cross-regulation exists between ERK and PIMT in regards to their activation and expression during the EMT.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
September 2011